Obesity and Appetite

Question 1

waist circumference is a surrogate measurement for _______

Answer 1

visceral adipose tissue, which is associated with increased risk for metabolic complications of obesity

[recall there is less risk associated with subcutaneous adipose]

Question 2

what is the effect of the endocannabinoid system on body mass regulation?

Answer 2

endocannabinoids: naturally synthesized, bind same receptors as THC throughout CNS

increase appetite/ reduce satiety, increase visceral fat, glucose uptake, and lipogenesis (stimulate PPAR-y excretion and LPL)

Question 3

from what tissue is leptin secreted from and what is its function?

Answer 3

peptide hormone secreted by white adipose, serum leptin is directly proportional to amount of triglycerides stored in adipose

decreases appetite and increases energy expenditure to regulate balance between food intake and energy storage

(leptin resistance is component of common obesity, corrects with weight loss)

Question 4

what are the clinical features of complete leptin deficiency?

Answer 4

early onset severe obesity and hyperphagia with constant food-seeking and reduced energy expenditure

—> hyperinsulinemia, liver steatosis
—> hypogonadotropic hypogonadism
—> recurrent bacterial infections

Question 5

where is ghrelin produced and what is its function?

Answer 5

produced in stomach and duodenum, ligand for GHS-R (growth hormone secretogogue receptor)

increases during fasting to stimulate appetite

[ghrelin makes you eat like a gremlin, or ghrelin is making your stomach growl]

Question 6

from where are GLP-1 and GIP (incretins) produced?

Answer 6

GLP-1 = glucagon like peptide
GIP = gastric inhibitory peptide

produced by enteroendocrine cells in the small intestine, increase pancreatic insulin secretion

levels increase following a meal, suppress appetite and food intake (delay gastric emptying)

Question 7

which 2 nuclei of the hypothalamus are important for appetite regulation?

Answer 7

1. paraventricular nucleus
2. arcuate nucleus

Question 8

what is the function of the POMC neurons found within the hypothalamus as it relates to appetite and energy intake?

Answer 8

POMC (Pro-Opio-Melano-Cortin) neurons in the arcuate nucleus produce alpha-MSH (melanocyte stimulating hormone)

alpha-MSH binds MC4R receptors on neurons in the paraventricular nucleus —> decrease appetite

Question 9

what is the function of neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons within the hypothalamus?

Answer 9

NPY and AgRP neurons within the arcuate nucleus work together to stimulate appetite

NPY via direct appetite stimulation, AgRP via inhibition of MSH (secreted by POMC neurons, decrease appetite) in paraventricular nucleus

Question 10

which of the following neuron types within the hypothalamus function to DECREASE appetite?
a. NPY
b. POMC
c. AgRP

Answer 10

b. POMC neurons decrease appetite

NPY and AgRP neurons increase appetite

Question 11

what is the effect of leptin on alpha-MSH levels?

Answer 11

leptin levels are proportional to stored triglycerides, and high leptin levels inhibit appetite

recall POMC neurons in the hypothalamus secrete alpha-MSH, which binds MC4R receptors in supraventricular nucleus to decrease appetite

therefore, increased leptin signaling increases alpha-MSH levels

Question 12

what is the effect of ghrelin on the following hypothalamic neuron types?
a. POMC
b. NPY
c. AgRP

Answer 12

recall ghrelin stimulates appetite

a. POMC - inhibit (secretes alpha-MSH to suppress appetite)
b. NPY - ACTIVATE (directly stimulates appetite)
c. AgRP - ACTIVATE (blocks alpha-MSH from POMC)

Question 13

on which hypothalamic neurons do GLP-1 and GIP act on to decrease appetite and food intake?

Answer 13

GLP-1 and GIP (incretins) activate POMC neurons in the arcuate nucleus, which secrete alpha-MSH to decrease appetite and food intake

Question 14

what 5 criteria define if a patient has metabolic syndrome?

Answer 14

patient has metabolic syndrome if 3/5 of these criteria are met:

1. high waist circumference —> central obesity (surrogate measure for visceral adipose)
2. elevated triglycerides
3. reduced HDL
4. elevated fasting glucose
5. elevated BP

Question 15

what reproductive disorder is associated with metabolic syndrome?

Answer 15

polycystic ovary syndrome (PCOS) - HIGHLY associated with insulin resistance and metabolic syndrome

PCOS patients 2-4x more likely to have metabolic syndrome

Question 16

waist circumference is a surrogate for _____

Answer 16

visceral adiposity (and therefore increased risk for metabolic syndrome and diabetes mellitus)

Question 17

what kind of drugs are Liraglutide, Semaglutide, and Tirzepatide?

Answer 17

GLP-1 (incretin) receptor agonists developed for glycemic control and found to be really great for weight loss

semaglutide = Ozempic or Wegovy (brand names)
tirzepatide = Mounjaro (brand name)